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Increasing rates of simultaneous heart-kidney (SHK) transplant in the United States exacerbate the overall shortage of deceased donor kidneys (DDK). Current allocation policy does not impose constraints on SHK eligibility, and how best to do so remains unknown. We apply a decision-analytic model to evaluate options for heart transplant (HT) candidates with comorbid kidney dysfunction. We compare SHK with a "Safety Net" strategy, in which DDK transplant is performed 6 months after HT, only if native kidneys do not recover. We identify patient subsets for whom SHK using a DDK is efficient, considering the quality-adjusted life year (QALY) gains from DDKs instead allocated for kidney transplant-only. For an average-aged candidate with a 50% probability of kidney recovery after HT-only, SHK produces 0.64 more QALYs than Safety Net at a cost of 0.58 more kidneys used. SHK is inefficient in this scenario, producing fewer QALYs per DDK used (1.1) than a DDK allocated for KT-only (2.2). SHK is preferred to Safety Net only for candidates with a lower probability of native kidney recovery (24%-38%, varying by recipient age). This finding favors the implementation of a Safety Net provision and should inform the establishment of objective criteria for SHK transplant eligibility.

A potential solution to the deceased donor organ shortage is to expand donor acceptability criteria. The procurement cost implications of using nonstandard donors is unknown. Using 5 years of US organ procurement organization (OPO) data, we built a cost function model to make cost projections: the total cost was the dependent variable; production outputs, including the number of donors and organs procured, were the independent variables. In the model, procuring one kidney or procuring both kidneys from double/en bloc transplantation from a single-organ donor resulted in a marginal cost of $55 k (95% confidence interval [CI] $28 k, $99 k) per kidney, and procuring only the liver from a single-organ donor results in a marginal cost of $41 k (95% CI $12 k, $69 k) per liver. Procuring two kidneys for two candidates from a donor lowered the marginal cost to $36 k (95% CI $22 k, $66 k) per kidney, and procuring two kidneys and a liver lowers the marginal cost to $24 k (95% CI $17 k, $45 k) per organ. Economies of scale were observed, where high OPO volume was correlated with lower costs. Despite higher cost per organ than for standard donors, kidney transplantation from nonstandard donors remained cost-effective based on contemporary US data.

OBJECTIVE The present systematic review and pooled analysis aims to assess the incidence and risk factors for the development of retrograde ejaculation (RE) following first-time open anterior lumbar surgery. METHODS A systematic MEDLINE review via PubMed was performed, identifying 130 clinical papers relating to the topic. Eighteen publications were selected according to predetermined inclusion and exclusion criteria and were used to determine the incidence of RE. Only the publications that provided data on surgical risk factors present specifically in the men in the study were included in the analysis of risk factors. RESULTS Of the 2503 men included, there were 57 reported events of RE (2.3%). Of the cases for which long-term data were provided, 45.8% had resolved by final follow-up. There was a statistically significant increased risk associated with a transperitoneal as opposed to a retroperitoneal approach (8.6% vs 3.2%), as well as with the use of recombinant human bone morphogenetic protein–2 (rhBMP-2) in anterior lumbar interbody fusion (ALIF) as opposed to ALIF with bone graft or arthroplasty in controls (5.0% vs 1.8%). However, when excluding from analysis the patients operated on prior to the FDA’s 2008 warning that commented on the drug’s neuroinflammatory properties, there was no significant difference in rates of RE in patients receiving rhBMP-2 versus the control group (2.4% vs 2.5%). There was no significant difference in risk based on single- versus multilevel procedure or on ALIF versus arthroplasty. CONCLUSIONS In a pooled analysis of currently published data on men undergoing first-time open anterior lumbar surgery, this study found an overall incidence of RE of 2.3%. Nearly half of these patients recovered, reporting resolution of symptoms anywhere between 3 months and 48 months. Analysis of risk factors was limited by a paucity of published literature segregating data by sex. However, there was an increased risk associated with rhBMP-2 only when including data collected prior to the FDA warning on its detrimental properties. The authors therefore posit that the risk of RE is probably overestimated in the literature, given that the vast majority of the data available were collected prior to this warning and given the subsequent implementation of precautions when handling rhBMP-2.

The coronavirus disease 2019 (COVID-19) pandemic has changed health care delivery across the United States. Few analyses have specifically looked at quantifying the financial impact of the pandemic on practicing neurosurgeons. A survey analysis was performed to address this need.A 19-question survey was distributed to practicing neurosurgeons in the United States and its territories. The questions evaluated respondents' assessments of changes in patient and procedural volume, salary and benefits, practice expenses, staffing, applications for government assistance, and stroke management. Responses were stratified by geographic region.The response rate was 5.1% (267/5224). Most respondents from each region noted a50% decrease in clinic volume. Respondents from the Northeast observed a 76% decrease in procedure volume, which was significantly greater than that of other regions (P = 0.003). Northeast respondents were also significantly more likely to have been reassigned to nonneurosurgical clinical duties during the pandemic (P0.001). Most respondents also noted decreased salary and benefits but experienced no changes in overall practice expenses. Most respondents did not experience significant reductions in nursing or midlevel staffing. These trends were not significantly different between regions.The COVID-19 pandemic has led to decreases in patient and procedural volume and physician compensation despite stable practice expenses. Significantly more respondents in the Northeast region noted decreases in procedural volume and reassignment to nonneurosurgical COVID-related medical duties. Future analysis is necessary as the pandemic evolves and the long-term clinical and economic implications become clear.

Patient-reported outcome measures such as the Pediatric Eye Questionnaire (PedEyeQ) are increasingly recognized as important in healthcare assessment. Defining normal PedEyeQ thresholds would allow classification of individual children as having reduced versus normal domain scores. We prospectively enrolled visually normal children (aged 0-17 years; n = 310) to calculate normal PedEyeQ domain thresholds. In addition, 48 children with bilateral visual impairment (VI; best-eye acuity worse than 20/70 or 20/70 or better with limited visual fields) were enrolled for validation. The Child PedEyeQ (four domains) was completed by 5- to 17-year-olds. Parents completed Proxy (five domains) and Parent PedEyeQ (four domains). Each domain was Rasch scored (converted to 0-100); normal thresholds were defined as the 5th percentile of scores in visually normal controls. For Child 5-11 PedEyeQ, 39%-78% of VI children had reduced domain scores, and 88%-100% for 12- to 17-year-olds. For Proxy PedEyeQ, proportions ranged from 55% to 100% and for Parent PedEyeQ ≥83% had reduced scores. High prevalence of reduced PedEyeQ domain scores in the VI cohort, validates the use of normal thresholds. Nevertheless, variability in child self-reporting creates challenges for identifying individual 5- to 11-year-olds with reduced scores.

ObjectiveTo evaluate the efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with active ankylosing spondylitis (AS).MethodsThis phase III, multicenter, double-blind, placebo-controlled study (ClinicalTrials.gov: NCT01583374) randomized patients with active AS (1:1:1) to placebo, apremilast 20 mg twice daily, or apremilast 30 mg twice daily for 24 weeks, followed by a long-term extension phase (up to 5 yrs). The primary endpoint was Assessment of the Spondyloarthritis international Society 20 (ASAS20) response at Week 16. The effect of treatment on radiographic outcomes after 104 weeks was assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS).ResultsIn total, 490 patients with active AS were randomized in the study (placebo: n = 164; apremilast 20 mg twice daily: n = 163; apremilast 30 mg twice daily: n = 163). The primary endpoint of ASAS20 response at Week 16 was not met (placebo: 37%; apremilast 20 mg twice daily: 35%; apremilast 30 mg twice daily: 33%; P = 0.44 vs placebo). At Week 104, mean (SD) changes from baseline in mSASSS were 0.83 (3.6), 0.98 (2.2), and 0.57 (1.9) in patients initially randomized to placebo, apremilast 20 mg twice daily, and apremilast 30 mg twice daily, respectively. The most frequently reported adverse events through Week 104 were diarrhea, nasopharyngitis, upper respiratory infection, and nausea.ConclusionNo clinical benefit was observed with apremilast treatment in patients with active AS. The safety and tolerability of apremilast were consistent with its known profile.

Background In the phase III KEYNOTE-189 study (NCT02578680), pembrolizumab plus pemetrexed and platinum-based chemotherapy (pemetrexed–platinum) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with previously untreated metastatic nonsquamous non-small-cell lung cancer (NSCLC) versus placebo plus pemetrexed–platinum. We report updated efficacy outcomes from the protocol-specified final analysis, including outcomes in patients who crossed over to pembrolizumab from pemetrexed–platinum and in patients who completed 35 cycles (∼2 years) of pembrolizumab. Patients and methods Eligible patients were randomized 2 : 1 to receive pembrolizumab 200 mg (n = 410) or placebo (n = 206) every 3 weeks (for up to 35 cycles, ∼2 years) plus four cycles of pemetrexed (500 mg/m2) and investigators’ choice of cisplatin (75 mg/m2) or carboplatin (area under the curve 5 mg·min/ml) every 3 weeks, followed by pemetrexed until progression. Patients assigned to placebo plus pemetrexed–platinum could cross over to pembrolizumab upon progression if eligibility criteria were met. The primary endpoints were OS and PFS. Results After a median follow-up of 31.0 months, pembrolizumab plus pemetrexed–platinum continued to improve OS [hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.46-0.69] and PFS (HR, 0.49; 95% CI, 0.41-0.59) over placebo plus pemetrexed–platinum regardless of programmed death-ligand 1 expression. Objective response rate (ORR) (48.3% versus 19.9%) and time to second/subsequent tumor progression on next-line treatment (PFS2; HR, 0.50; 95% CI, 0.41-0.61) were improved in patients who received pembrolizumab plus pemetrexed–platinum. Eighty-four patients (40.8%) from the placebo plus pemetrexed–platinum group crossed over to pembrolizumab on-study. Grade 3-5 adverse events occurred in 72.1% of patients receiving pembrolizumab plus pemetrexed–platinum and 66.8% of patients receiving placebo plus pemetrexed–platinum. Fifty-six patients completed 35 cycles (∼2 years) of pembrolizumab; ORR was 85.7% and 53 (94.6%) were alive at data cut-off. Conclusions Pembrolizumab plus pemetrexed–platinum continued to show improved efficacy outcomes compared with placebo plus pemetrexed–platinum, with manageable toxicity. These findings support first-line pembrolizumab plus pemetrexed–platinum in patients with previously untreated metastatic nonsquamous NSCLC.

Summary Background PD-1 and PD-L1 inhibitors are active in metastatic urothelial carcinoma, but positive randomised data supporting their use as a first-line treatment are lacking. In this study we assessed outcomes with first-line pembrolizumab alone or combined with chemotherapy versus chemotherapy for patients with previously untreated advanced urothelial carcinoma. Methods KEYNOTE-361 is a randomised, open-label, phase 3 trial of patients aged at least 18 years, with untreated, locally advanced, unresectable, or metastatic urothelial carcinoma, with an Eastern Cooperative Oncology Group performance status of up to 2. Eligible patients were enrolled from 201 medical centres in 21 countries and randomly allocated (1:1:1) via an interactive voice-web response system to intravenous pembrolizumab 200 mg every 3 weeks for a maximum of 35 cycles plus intravenous chemotherapy (gemcitabine [1000 mg/m2] on days 1 and 8 and investigator's choice of cisplatin [70 mg/m2] or carboplatin [area under the curve 5] on day 1 of every 3-week cycle) for a maximum of six cycles, pembrolizumab alone, or chemotherapy alone, stratified by choice of platinum therapy and PD-L1 combined positive score (CPS). Neither patients nor investigators were masked to the treatment assignment or CPS. At protocol-specified final analysis, sequential hypothesis testing began with superiority of pembrolizumab plus chemotherapy versus chemotherapy alone in the total population (all patients randomly allocated to a treatment) for the dual primary endpoints of progression-free survival (p value boundary 0·0019), assessed by masked, independent central review, and overall survival (p value boundary 0·0142), followed by non-inferiority and superiority of overall survival for pembrolizumab versus chemotherapy in the patient population with CPS of at least 10 and in the total population (also a primary endpoint). Safety was assessed in the as-treated population (all patients who received at least one dose of study treatment). This study is completed and is no longer enrolling patients, and is registered at ClinicalTrials.gov , number NCT02853305 . Findings Between Oct 19, 2016 and June 29, 2018, 1010 patients were enrolled and allocated to receive pembrolizumab plus chemotherapy (n=351), pembrolizumab monotherapy (n=307), or chemotherapy alone (n=352). Median follow-up was 31·7 months (IQR 27·7–36·0). Pembrolizumab plus chemotherapy versus chemotherapy did not significantly improve progression-free survival, with a median progression-free survival of 8·3 months (95% CI 7·5–8·5) in the pembrolizumab plus chemotherapy group versus 7·1 months (6·4–7·9) in the chemotherapy group (hazard ratio [HR] 0·78, 95% CI 0·65–0·93; p=0·0033), or overall survival, with a median overall survival of 17·0 months (14·5–19·5) in the pembrolizumab plus chemotherapy group versus 14·3 months (12·3–16·7) in the chemotherapy group (0·86, 0·72–1·02; p=0·0407). No further formal statistical hypothesis testing was done. In analyses of overall survival with pembrolizumab versus chemotherapy (now exploratory based on hierarchical statistical testing), overall survival was similar between these treatment groups, both in the total population (15·6 months [95% CI 12·1–17·9] with pembrolizumab vs 14·3 months [12·3–16·7] with chemotherapy; HR 0·92, 95% CI 0·77–1·11) and the population with CPS of at least 10 (16·1 months [13·6–19·9] with pembrolizumab vs 15·2 months [11·6–23·3] with chemotherapy; 1·01, 0·77–1·32). The most common grade 3 or 4 adverse event attributed to study treatment was anaemia with pembrolizumab plus chemotherapy (104 [30%] of 349 patients) or chemotherapy alone (112 [33%] of 342 patients), and diarrhoea, fatigue, and hyponatraemia (each affecting four [1%] of 302 patients) with pembrolizumab alone. Six (1%) of 1010 patients died due to an adverse event attributed to study treatment; two patients in each treatment group. One each occurred due to cardiac arrest and device-related sepsis in the pembrolizumab plus chemotherapy group, one each due to cardiac failure and malignant neoplasm progression in the pembrolizumab group, and one each due to myocardial infarction and ischaemic colitis in the chemotherapy group. Interpretation The addition of pembrolizumab to first-line platinum-based chemotherapy did not significantly improve efficacy and should not be widely adopted for treatment of advanced urothelial carcinoma. Funding Merck Sharp and Dohme, a subsidiary of Merck, Kenilworth, NJ, USA.

Pancreatic angiosarcoma is an exceedingly rare malignancy accounting for

There is a lack of normative data for children tested with the electronic Early Treatment for Diabetic Retinopathy Study (E-ETDRS) protocol. In the current cross-sectional study, the mean best-corrected normal and 95% lower tolerance limit for E-ETDRS visual acuity by year in children 7-12 years of age was measured. Our objective was to provide a large normative data set for E-ETDRS visual acuity in children for use in clinical management and clinical trials.

Objective:Peripheral artery disease (PAD) is an atherothrombotic disease of the lower limbs with substantial morbidity and mortality. We used next-generation sequencing to identify genome-wide expression signatures associated with prevalent PAD and its outcomes.Approach and Results:We performed whole blood RNA sequencing among patients with severe symptomatic PAD undergoing lower extremity revascularization and controls. Dysregulated pathways and blood transcriptional modules were identified by comparing patients with PAD (n=42) to age- and sex-matched controls (N=29). The identified signature was compared in patients with PAD before LER with or without incident major adverse cardiac or limb events (MACLE). A novel microRNA associated with prevalent PAD and incident MACLE was then evaluated in a mouse hindlimb ischemia model. One hundred twenty-seven transcripts were differentially expressed (77 upregulated and 50 downregulated; adjustedP0.5) and analyzed using weighted gene co-expression network analysis. Weighted gene co-expression network analysis revealed blood modules enriched for immune activation, secretory granules, and coagulation in patients with PAD. Of these 127 differentially expressed transcripts, 40 were significantly associated with MACLE (log-rank false discovery rate Conclusions:A whole blood transcript signature identified patients with symptomatic PAD and PAD patients at increased risk of MACLE. A previously uncharacterized transcript microRNA-4477b was overexpressed in prevalent PAD, incident MACLE, and in a mouse hindlimb ischemia model. Our novel transcriptomic signature provides insight into potential mechanisms of patients with severe symptomatic PAD.

ObjectiveDetermine the effectiveness of intraosseous basivertebral nerve radiofrequency neurotomy for the treatment of chronic low back pain with type 1 or 2 Modic changes.DesignSystematic review.PopulationPersons aged ≥18 years with chronic low back pain with type 1 or 2 Modic changes.InterventionIntraosseous basivertebral nerve radiofrequency neurotomyComparisonSham, placebo procedure, active standard care treatment, or none.OutcomesThe primary outcome of interest was the proportion of individuals with ≥50% pain reduction. Secondary outcomes included ≥10-point improvement in function as measured by Oswestry Disability Index as well as ≥2-point reduction in pain score on the Visual Analog Scale or Numeric Rating Scale, and decreased use of pain medication.MethodsThree reviewers independently assessed publications before May 15, 2020, in MEDLINE and Embase and the quality of evidence was evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation framework.ResultsOf the 725 publications screened, seven publications with 321 participants were ultimately included. The reported 3-month success rate for ≥50% pain reduction ranged from 45% to 63%. Rates of functional improvement (≥10-point Oswestry Disability Index improvement threshold) ranged from 75% to 93%. For comparison to sham treatment, the relative risk of treatment success defined by ≥50% pain reduction and ≥10-point Oswestry Disability Index improvement was 1.25 (95% confidence interval [CI]: .88—1.77) and 1.38 (95% CI: 1.10—1.73), respectively. For comparison to continued standard care treatment the relative risk of treatment success defined by ≥50% pain reduction and ≥10-point Oswestry Disability Index improvement was 4.16 (95% CI: 2.12–8.14) and 2.32 (95% CI: 1.52–3.55), respectively.ConclusionsThere is moderate-quality evidence that suggests this procedure is effective in reducing pain and disability in patients with chronic low back pain who are selected based on type 1 or 2 Modic changes, among other inclusion and exclusion criteria used in the published literature to date. Success of the procedure appears to be dependent on effective targeting of the BVN. Non-industry funded high-quality, large prospective studies are needed to confirm these findings.

BACKGROUND CONTEXT Positive psychosocial factors early after surgery, such as resilience and self-efficacy, may be important characteristics for informing individualized postoperative care. PURPOSE To examine the association of early postoperative resilience and self-efficacy on 12-month physical function, pain interference, social participation, disability, pain intensity, and physical activity after lumbar spine surgery. STUDY DESIGN/SETTING Pooled secondary analysis of prospectively collected trial data from two academic medical centers. PATIENT SAMPLE Two hundred and forty-eight patients who underwent laminectomy with or without fusion for a degenerative lumbar condition. OUTCOME MEASURES Physical function, pain inference, and social participation (ability to participate in social roles and activities) were measured using the Patient Reported Outcomes Measurement Information System. The Oswestry Disability Index, Numeric Rating Scale, and accelerometer activity counts were used to measure disability, pain intensity, and physical activity, respectively. METHODS Participants completed validated outcome questionnaires at 6 weeks (baseline) and 12 months after surgery. Baseline positive psychosocial factors included resilience (Brief Resilience Scale) and self-efficacy (Pain Self-Efficacy Questionnaire). Multivariable linear regression analyses were used to assess the associations between early postoperative psychosocial factors and 12-month outcomes adjusting for age, sex, study site, randomized group, fusion status, fear of movement (Tampa Scale for Kinesiophobia), and outcome score at baseline. This study was funded by Patient-Centered Outcomes Research Institute and Foundation for Physical Therapy Research. There are no conflicts of interest. RESULTS Resilience at 6 weeks after surgery was associated with 12-month physical function (unstandardized beta=1.85 [95% confidence interval [CI]: 0.29; 3.40]), pain interference (unstandardized beta=−1.80 [95% CI: −3.48; −0.12]), social participation (unstandardized beta=2.69 [95% CI: 0.97; 4.41]), and disability (unstandardized beta=−3.03 [95% CI: −6.04; −0.02]). Self-efficacy was associated with 12-month disability (unstandardized beta=−0.21 [95% CI: −0.37; −0.04]. CONCLUSIONS Postoperative resilience and pain self-efficacy were associated with improved 12-month patient-reported outcomes after spine surgery. Future work should consider how early postoperative screening for positive psychosocial characteristics can enhance risk stratification and targeted rehabilitation management in patients undergoing spine surgery.

Introduction: Coronary computed tomography angiography (CCTA) is emerging as an important noninvasive testing modality for coronary angiography. The performance characteristic of CCTA in patients with advanced kidney disease is unknown. Methods: We performed a systematic review and meta-analysis of studies specifically investigating the sensitivity and specificity of CCTA compared to coronary angiogram as a reference standard in patients with advanced kidney disease, defined as dialysis dependence or nearing kidney transplantation. Two independent investigators assessed studies for inclusion/exclusion, quality, and characteristics, while a third investigator adjudicated. Results: We identified 4 studies including a total of 217 patients, of whom 159 were dialysis dependent. Three of the 4 studies had a high risk of bias in patient selection and study flow, while 1 study rated low in all areas of bias. The studies were heterogeneous in their patient selection and CCTA protocol but consistent in their definition of obstructive coronary artery disease. The pooled sensitivity and specificity for CCTA were 0.96 (0.87–0.99) and 0.66 (0.57–0.74), respectively. When we restricted the analysis to dialysis-dependent patients, the pooled sensitivity and specificity for CCTA were 0.99 (0.74–1.00) and 0.67 (0.49–0.82), respectively. Conclusions: Based on limited data, CCTA appears to have comparable sensitivity but lower specificity relative to the non-kidney disease population.

Purpose of review Simultaneous heart-liver (SHL) transplants are only a small proportion of overall heart and liver transplantation, they have been increasing in frequency and thus challenge the equitable allocation of organs. Recent findings The incidence of SHL transplants is reviewed along with the outcomes of SHL transplants and their impact on the waitlist, particularly in the context of solitary heart and liver transplantation. The ethical implications, most importantly the principles of utility and equity, of SHL transplant are addressed. In the context of utility, the distinction of a transplant being life-saving versus life-enhancing is investigated. The risk of hepatic decompensation for those awaiting both solitary and combined organ transplantation is an important consideration for the principle of equity. Lastly, the lack of standardization of programmatic approaches to SHL transplant candidates, the national approach to allocation, and the criteria by which programs are evaluated are reviewed. Summary As with all multiorgan transplantation, SHL transplantation raises ethical issues of utility and equity. Given the unique patient population, good outcomes, lack of alternatives, and overall small numbers, we feel there is continued ethical justification for SHL, but a more standardized nationwide approach to the evaluation, listing, and allocation of organs is warranted.

STUDY DESIGN Secondary analysis of randomized controlled trial data. OBJECTIVE The aim of this study was to examine whether preoperative physical performance is an independent predictor of patient-reported disability and pain at 12 months after lumbar spine surgery. SUMMARY OF BACKGROUND DATA Patient-reported outcome measures (PROMs) are commonly used to assess clinical improvement after lumbar spine surgery. However, there is evidence in the orthopedic literature to suggest that PROMs should be supplemented with physical performance tests to accurately evaluate long-term outcomes. METHODS A total of 248 patients undergoing surgery for degenerative lumbar spine conditions were recruited from two institutions. Physical performance tests (5-Chair Stand and Timed Up and Go) and PROMs of disability (Oswestry Disability Index: ODI) and back and leg pain (Brief Pain Inventory) were assessed preoperatively and at 12 months after surgery. RESULTS Physical performance tests and PROMs significantly improved over 12 months following lumbar spine surgery (P

Background context The North American Spine Society's (NASS) Evidence Based Clinical Guideline for the Diagnosis and Treatment of Low Back Pain features evidence-based recommendations for diagnosing and treating adult patients with nonspecific low back pain. The guideline is intended to reflect contemporary treatment concepts for nonspecific low back pain as reflected in the highest quality clinical literature available on this subject as of February 2016. PURPOSE The purpose of the guideline is to provide an evidence-based educational tool to assist spine specialists when making clinical decisions for adult patients with nonspecific low back pain. This article provides a brief summary of the evidence-based guideline recommendations for diagnosing and treating patients with this condition. Study design This is a guideline summary review. Methods This guideline is the product of the Low Back Pain Work Group of NASS’ Evidence-Based Clinical Guideline Development Committee. The methods used to develop this guideline are detailed in the complete guideline and technical report available on the NASS website. In brief, a multidisciplinary work group of spine care specialists convened to identify clinical questions to address in the guideline. The literature search strategy was developed in consultation with medical librarians. Upon completion of the systematic literature search, evidence relevant to the clinical questions posed in the guideline was reviewed. Work group members utilized NASS evidentiary table templates to summarize study conclusions, identify study strengths and weaknesses, and assign levels of evidence. Work group members participated in webcasts and in-person recommendation meetings to update and formulate evidence-based recommendations and incorporate expert opinion when necessary. The draft guideline was submitted to an internal and external peer review process and ultimately approved by the NASS Board of Directors. Results Eighty-two clinical questions were addressed, and the answers are summarized in this article. The respective recommendations were graded according to the levels of evidence of the supporting literature. Conclusions The evidence-based clinical guideline has been created using techniques of evidence-based medicine and best available evidence to aid practitioners in the diagnosis and treatment of adult patients with nonspecific low back pain. The entire guideline document, including the evidentiary tables, literature search parameters, literature attrition flowchart, suggestions for future research, and all of the references, is available electronically on the NASS website at https://www.spine.org/ResearchClinicalCare/QualityImprovement/ClinicalGuidelines.aspx

Background Chin-on-chest kyphotic cervical deformity can be debilitating. Surgical deformity correction serves to decompress neural elements and restore lordosis. This can be achieved through multiple osteotomies with instrumentation and fusion, sometimes requiring a staged approach. Such procedures carry a high risk of neurologic injury. Here we present examples of transient neurologic dysfunction not previously reported in the common literature. Case Description The authors present 3 patients who underwent extreme cervical deformity correction for chin-on-chest deformity. Deformity correction in all cases was obtained through multiple osteotomies with multilevel cervicothoracic posterior instrumentation and arthrodesis. On postoperative examination, all 3 patients developed transient ataxia, dysmetria, and decreased proprioception in all 4 extremities—examination findings consistent with dorsal column dysfunction. All symptoms resolved within 2–3 weeks postoperatively. Conclusions Incomplete spinal cord syndromes such as posterior cord syndrome can be caused by compression or stretching of the ascending dorsal spinal tracts. Considering the large degree of correction obtained, we hypothesize the resulting shortening of the dorsal columns as the pathomechanism. Providers should be aware, and patients should be counseled preoperatively that these symptoms may occur. If these symptoms are present postoperatively, appropriate diligence is warranted with the understanding that these deficits may be transient.

Background: Debate on whether to stop fusion at L5 or to extend fusion to S1 in a long spinal construct has been a controversial topic in spine surgery. Fewer data are available to support whether to include a prior solid fusion at L4–L5 or to extend to S1 during a proximal extension of fusion to T10. The purpose of this review is to report and discuss 2 cases of L5 vertebra fracture after proximal extension of solid L4–L5 fusion to T10 and to provide a guideline to surgeons based on the available literature. Methods: Case report and literature review. Results: Literature review identified multiple publications with levels of evidence from level 2 to level 4. Advanced L5–S1 degeneration with long-segment fusion to L5 is reported to be greater than 60% with a new rate of symptom development approaching 20%–25%. There is no prior literature specific to L5 fracture development after thoracic lumbar fusion with the lowest instrumented level at a fused L4–L5 segment. Reoperation rate is not consistently affected by the lowest instrumented vertebral level L5 versus sacrum/ilium. Conclusions: Literature review is inconclusive as to the need to include the lumbosacral junction when performing a proximal extension of fusion from L5 to the thoracic spine, especially during a revision adult deformity surgery. Stress of the long lever arm of a long-segment thoracolumbar fusion above a prior solid L4–L5 fusion could cause the L5 vertebra to split in the coronal plane, resulting in vertebral body fracture even with a mildly degenerated disc at L5–S1 prior to surgery. Level of Evidence: 4.

Introduction Immune-complex deposition in the transplanted kidney can present as well-phenotyped recurrent or de novo glomerular disease. However, a subset, herein termed immune-complex glomerulopathy not otherwise specified (ICG-NOS), defies classification. We quantified, categorized, and characterized cases of transplant ICG-NOS occurring at a single US academic medical center. Methods We retrospectively reviewed our single-institution pathology database (July 2007–July 2018) to identify and categorize all cases of immune-complex deposition in kidney allografts (based on immunofluorescence microscopy). We extracted clinicopathologic and outcome data for ICG-NOS (i.e., immune complex deposition not conforming to any well-characterized glomerular disease entity). Results Of 104 patients with significant immune deposits, 28 (27%) were classified as ICG-NOS. We created 5 mutually exclusive ICG-NOS categories: Full-house, Quasi-full-house, IgA-rich, C1q-rich, and C1q-poor. Overall, 16 (57%) patients met criteria for definite or possible allograft rejection, including 9 (32%) with antibody-mediated rejection (ABMR), 3 (11%) suspicious for ABMR, 1 (4%) with T-cell–mediated rejection (TCMR), and 9 (32%) with borderline TCMR. After a median follow-up of 2.3 (range, 0.1–14.0) years after biopsy, 7 (25%) allografts had failed and an additional 8 (29%) had persistent renal dysfunction (hematuria, 14%; proteinuria, 21%; and estimated glomerular filtration rate, Graphical abstract

Background The Centers for Disease Control and Prevention have declared that the United States is amidst a continuing opioid epidemic, with drug overdose–related death tripling between 1999 and 2014. Among the 47,055 overdose-related deaths that occurred in 2014, 28,647 (60.9%) of them involved an opioid. Methods To determine if there are specific trends in opioid prescribing practices of specific groups of surgeons to better describe any regional or subspecialty trends that exist, the Part D Prescriber Public Use File was used to evaluate all prescription drug orders for Medicare beneficiaries with a Part D prescription drug plan for the 2015 calendar year. Only those providers with the specialty description corresponding to a surgical specialty were included in this study, using the provider's Part B claims. Results A total of 65,277,932 claims made to Part D by 90,253 surgeons in the 2015 service year were analyzed in this study, demonstrating statistically significant differences in the opioid prescribing practices of surgeons from different states, cities, practice settings, and subspecialties (P, Highlights • A total of 47,055 overdose deaths occurred in 2014; 28,647 (60.9%) of them involved an opioid. • Medicare Part D was queried for information on prescription drug events. • A total of 65,277,932 claims by 90,253 surgeons in the 2015 service year were analyzed. • Prescribing practices differed from surgeons based on states and subspecialties. • Opioid medication claims cost the health care system $133,091,997.81 in benefits.

BACKGROUND: Organ scarcity continues in solid organ transplantation, such that the availability of organs limits the number of people able to benefit from transplantation. Medical advancements in managing end-stage organ disease have led to an increasing demand for multi-organ transplant, wherein a patient with multi-organ disease receives more than one organ from the same donor. Current allocation schemes give priority to multi-organ recipients over single-organ transplant recipients, which raises ethical questions regarding equity and utility. METHODS: We use simultaneous liver-kidney (SLK) transplant, a type of multi-organ transplant, as a case study to examine the tension between equity and utility in multi-organ allocation. We adapt the health economics willingness-to-pay threshold to a solid organ transplant setting by coining a new metric: the willingness-to-transplant (WTT) threshold. RESULTS: We demonstrate how the WTT threshold can be used to evaluate different SLK allocation strategies by synthesizing utility and equity perspectives. CONCLUSIONS: We submit that this new framework enables us to distill the question of SLK allocation down to: what is the minimum amount of benefit we require from a deceased donor kidney to allocate it for a particular indication? Addressing the above question will prove helpful to devising a rational system of SLK allocation and is applicable to other transplant settings.

PURPOSE: To evaluate the recently developed Pediatric Eye Questionnaire (PedEyeQ) in visually impaired and visually normal children, as an initial validation of the PedEyeQ. DESIGN: Questionnaire validation study METHODS: 48 children with visual impairment (retinal, cortical, and corneal conditions) and 59 visually normal controls were enrolled at two centers. Five- to 17-year-old children completed the Child PedEyeQ (5–11 and 12–17 year-old versions), and parents completed the Proxy PedEyeQ (0–4, 5–11, 12–17 year-old versions) and the Parent PedEyeQ. Rasch scores were calculated, by age group, for each distinct domain within each age-specific PedEyeQ (converted to 0–100 for interpretation). Domains for the Child PedEyeQ are functional vision, bothered by eyes/vision, social, frustration/worry. Proxy PedEyeQ domains are: functional vision, bothered by eyes/vision, social, frustration/worry, eye-care. Parent PedEyeQ domains are: impact on parent and family, worry about child’s eye condition, worry about child’s self-perception/interactions, worry about child’s functional vision. For each domain, median PedEyeQ scores were compared between visually impaired and visually normal cohorts. RESULTS: Child 5–11 and 12–17 PedEyeQ scores were significantly lower (worse) for visually impaired children than for controls for each domain (P

BACKGROUND AND OBJECTIVES: In December 2014, the Kidney Allocation System (KAS) was implemented to improve equity in access to transplantation, but preliminary studies in children show mixed results. Thus, we aimed to assess how the 2014 KAS policy change affected racial and ethnic disparities in pediatric kidney transplantation access and related outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective cohort study of children

Purpose To report a successful treatment of chronic rosacea associated ocular demodicosis with lid scrub containing terpinen-4-ol (T4O). Observations A 72-year old woman presented with recurrent and refractory ocular erythema, irritation, dryness, and photophobia despite conventional medical treatment (artificial tears, hypochlorous acid lid hygiene, doxycycline, and erythromycin) for 5 years. Examination revealed facial erythema, telangiectasias on cheeks, nose and lids, and cylindrical dandruff (CD) on bilateral upper and lower lashes. Epilation sampling confirmed demodicosis. After treatment with lid wipe containing T4O (Cliradex, Biotissue, Miami, FL) over face and lids, ocular discomfort, CD, facial and eyelid erythema, telangiectatic vessels were significantly reduced. Complete eradication of demodex mites and resolution of symptoms and signs lasted 8 months of follow-up. Conclusions This case suggests that T4O is effective in treating chronic rosacea associated ocular demodex blepharitis.

Background and objectives: In patients with kidney failure due to IgA nephropathy, IgA deposits can recur in a subsequent kidney transplant. The incidence, effect, and risk factors of IgA nephropathy recurrence is unclear, because most studies have been single center and sample sizes are relatively small.Design, setting, participants, & measurements: We performed a multicenter, international, retrospective study to determine the incidence, risk factors, and treatment response of recurrent IgA nephropathy after kidney transplantation. Data were collected from all consecutive patients with biopsy-proven IgA nephropathy transplanted between 2005 and 2015, across 16 “The Post-Transplant Glomerular Disease” study centers in Europe, North America, and South America.Results: Out of 504 transplant recipients with IgA nephropathy, recurrent IgA deposits were identified by kidney biopsy in 82 patients; cumulative incidence of recurrence was 23% at 15 years (95% confidence interval, 14 to 34). Multivariable Cox regression revealed a higher risk for recurrence of IgA deposits in patients with a pre-emptive kidney transplant (hazard ratio, 3.45; 95% confidence interval, 1.31 to 9.17) and in patients with preformed donorspecific antibodies (hazardratio, 2.59; 95%confidence interval, 1.09 to 6.19).Afterkidneytransplantation,development of de novo donor-specific antibodies was associated with subsequent higher risk of recurrence of IgA nephropathy (hazard ratio, 6.65; 95% confidence interval, 3.33 to 13.27). Immunosuppressive regimen was not associated with recurrent IgA nephropathy in multivariable analysis, including steroid use. Graft loss was higher in patients with recurrence of IgA nephropathy compared with patients without (hazard ratio, 3.69; 95% confidence interval, 2.04 to 6.66), resulting in 32% (95% confidence interval, 50 to 82) graft loss at 8 years after diagnosis of recurrence.Conclusions: In our international cohort, cumulative risk of IgA nephropathy recurrence increased after transplant and was associated with a 3.7-fold greater risk of graft loss.

Retrospective cohort study.The purpose of this investigation was to evaluate the regional variations in the use of nonoperative therapies in patients diagnosed with a lumbar intervertebral disc herniation 3 months prior to undergoing microdiscectomy surgery.Regional variations in the management of chronic pain conditions have been previously identified. Patients suffering from a lumbar intervertebral disc herniation are typically treated with a brief course of conservative management prior to attempting microdiscectomy surgery. Whether regional differences exist in the utilization or costs of maximum nonoperative therapy (MNT) remains unknown.Medical records from patients diagnosed with a lumbar intervertebral disc herniation undergoing 1, 2, or 3-level index microdiscectomy operations between 2007 and 2017 were gathered from the HORTHO insurance database consisting of private/commercially insured and Medicare Advantage beneficiaries. Patient regional designation was divided into Midwest, Northeast, South, and West territories and was derived from the insurance claim location. The utilization of MNT within 3 months after initial lumbar herniation diagnosis in adult patients was analyzed.Our population consisted of 13,106 patients who underwent primary index microdiscectomy surgery. Significant regional variation was identified in the nonoperative therapy failure rate (P0.0001), with the highest proportion of Midwest patients failing (2.7%). There were statistical differences in the regional distribution of patients utilizing NSAIDs (P0.0001), muscle relaxants (P0.0001), lumbar epidural steroid injections (P0.0001), physical therapy and occupational therapy sessions (P0.0001), chiropractor treatments (P0.0001), and emergency department services (P = 0.0049). The total direct cost associated with all MNT prior to microdiscectomy was $13,205,924, with 59.6% from the South, 31.1% from the Midwest, 8.3% from the West, and 1.1% from the Northeast.These findings indicate that regional differences exist in the utilization and costs of MNT of a lumbar intervertebral herniated disc prior to microdiscectomy surgery.3.

Purpose Alterations to mismatch repair (MMR) pathways are a known cause of cancer, particularly colorectal and endometrial carcinomas. Recently, checkpoint inhibitors have been approved for use in MMR-deficient cancers of any type (Prasad et al. in JAMA Oncol 4:157–158, 2018). Functional studies in breast cancer have shown associations between MMR loss, resistance to aromatase inhibitors and sensitivity to palbociclib (Haricharan et al. in Cancer Discov 7:1168–1183, 2017). Herein, we investigate the clinical meaning of MMR deficiency in breast cancer by immunohistochemical assessment of MSH2, MSH6, MLH1 and PMS2 on a large series of breast cancers linked to detailed biomarker and long-term outcome data. Methods Cases were classified as MMR intact when all four markers expressed nuclear reactivity, but MMR-deficient when at least one of the four biomarkers displayed loss of nuclear staining in the presence of positive internal stromal controls on the tissue microarray core. Results Among the 1635 cases with interpretable staining, we identified 31 (1.9%) as MMR-deficient. In our cohort, MMR deficiency was present across all major breast cancer subtypes, and was associated with high-grade, low-progesterone receptor expression and high tumor-infiltrating lymphocyte counts. MMR deficiency is significantly associated with inferior overall (HR 2.29, 95% CI 1.02–5.17, p = 0.040) and disease-specific survival (HR 2.71, 95% CI 1.00–7.35, p = 0.042) in the 431 estrogen receptor-positive patients who were uniformly treated with tamoxifen as their sole adjuvant systemic therapy. Conclusion Overall, this study supports the concept that breast cancer patients with MMR deficiency as assessed by immunohistochemistry may be good candidates for alternative treatment approaches such as immune checkpoint or CDK4 inhibitors.

Background Same-day surgery has been demonstrated to be a safe and cost-effective alternative to traditional inpatient surgery. Several studies have demonstrated no differences in the postoperative complication profile or 30-day hospital readmission rates with outpatient versus inpatient anterior cervical discectomy and fusion (ACDF). However, none of these studies compared the outcomes in elderly patients (aged >65 years) undergoing ACDF. Whether the results from previous studies can be applied to this subgroup pf patients remains unknown. The aim of the present study was to compare the 30-day hospital readmission rates for Medicare patients (aged >65 years) undergoing outpatient versus inpatient ACDF. Methods We performed a retrospective analysis of a Medicare database, including data from 17,421 patients. Of the 17,421 patients, 16,386 had undergone inpatient ACDF and 1035, outpatient ACDF. Age, sex, comorbidities, postoperative complications, readmission rates, and overall financial costs were compared between the 2 cohorts. Results In a Medicare sample (aged >65 years), inpatient ACDF was associated with a greater incidence of postoperative complications compared with outpatient ACDF. Outpatient surgery was associated with significantly lower rates of postoperative complications (urinary tract infection, surgical site infection, deep vein thrombosis, pulmonary embolism, and myocardial infarction) and significantly lower treatment costs (P ≤ 0.001). All-cause 30-day hospital readmission rates were also greater for inpatients (10.1% vs. 4%; P = 0.17). Conclusion The results from the present study suggest that outpatient ACDF appears to be safe and effective with low complication and readmission rates in a Medicare patient sample.

Background Ehlers-Danlos syndrome (EDS) is a group of rare congenital disorders of connective tissue that result in tissue fragility and joint hyperextensibility. Owing to its rarity, outcomes of pediatric spine surgery in patients with EDS are poorly characterized. Although it has been suggested that complication rates are high, few studies have characterized these complications. Methods Pediatric National Surgery Quality Improvement Program data from 2012–2016 were analyzed. Patients with EDS undergoing spine surgery were identified along with patients without EDS undergoing the same surgeries using International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes. Results Of 369,176 total patients, 279 were determined to have EDS. Of these, 56 patients underwent spine surgery; 46% were male and 54% were female (P = 0.108). Mean age at surgery was 11.59 years (P = 0.888) with a range of 1.77–17.33 years. The most common procedure was arthrodesis (n = 37). There were no differences in unplanned reoperations (n = 4, P = 0.119), wound infections or disruptions (n = 2, P = 0.670), or overall complications (n = 25, P = 0.751). Blood transfusions were required in 41% of patients with EDS, but this was not significant compared with patients without EDS undergoing the same procedures (n = 23, P = 0.580). The total amount of blood transfused (P = 0.508), length of hospital stay (P = 0.396), and total operative time (P = 0.357) were not different from control subjects. Conclusions Pediatric patients with EDS do not appear to be at a higher risk of bleeding or other complications during spine surgery as reported in past case series. This is the largest retrospective review of its kind that has been performed in this patient population.

Klippel-Feil syndrome (KFS) occurs due to failure of vertebral segmentation during development. Minimal research has been done to understand the prevalence of associated symptoms. Here, we report one of the largest collections of KFS patient data. Data were obtained from the CoRDS registry. Participants with cervical fusions were categorized into Type I, II, or III based on the Samartzis criteria. Symptoms and comorbidities were assessed against type and location of fusion. Seventy-five patients (60F/14M/1 unknown) were identified and classified as: Type I, n = 21(28%); Type II, n = 15(20%); Type III, n = 39(52%). Cervical fusion by level were: OC–C1, n = 17(22.7%), C1–C2, n = 24(32%); C2–C3, n = 42(56%); C3–C4, n = 30(40%); C4–C5, n = 42(56%); C5–C6, n = 32(42.7%); C6–C7, n = 25(33.3%); C7–T1, n = 13(17.3%). 94.6% of patients reported current symptoms and the average age when symptoms began and worsened were 17.5 (± 13.4) and 27.6 (± 15.3), respectively. Patients reported to have a high number of comorbidities including spinal, neurological and others, a high frequency of general symptoms (e.g., fatigue, dizziness) and chronic symptoms (limited range of neck motion [LROM], neck/spine muscles soreness). Sprengel deformity was reported in 26.7%. Most patients reported having received medication and invasive/non-invasive procedures. Multilevel fusions (Samartzis II/III) were significantly associated with dizziness (p = 0.040), the presence of LROM (p = 0.022), and Sprengel deformity (p = 0.036). KFS is associated with a number of musculoskeletal and neurological symptoms. Fusions are more prevalent toward the center of the cervical region, and less common at the occipital/thoracic junction. Associated comorbidities including Sprengel deformity may be more common in KFS patients with multilevel cervical fusions. These slides can be retrieved under Electronic Supplementary Material.

Study Design: Ambispective study with propensity matching. Objective: To assess the impact of cervical spondylolisthesis (CS) on clinical presentation and surgical outcome in patients with degenerative cervical myelopathy (DCM). Methods: A total of 458 magnetic resonance images (MRIs) from the AOSpine CSM-NA and CSM-I studies were reviewed and CS was identified. Patients with DCM were divided into 2 cohorts, those with CS and those without, and propensity matching was performed. Patient demographics, neurological and functional status at baseline and 2-year follow-up were compared. Results: Compared with nonspondylolisthesis (n = 404), CS patients (n = 54) were 8.8 years older ( P < .0001), presented with worse baseline neurological and functional status (mJOA [modified Japanese Orthopaedic Association Assessment Scale], P = .008; Nurick, P = .008; SF-36-PCS [Short Form–36 Physical Component Score], P = .01), more commonly presented with ligamentum flavum enlargement (81.5% vs 53.5%, P < .0001), and were less commonly from Asia ( P = .0002). Surgical approach varied between cohorts ( P = .0002), with posterior approaches favored in CS (61.1% vs 37.4%). CS patients had more operated levels (4.3 ± 1.4 vs 3.6 ± 1.2, P = .0002) and tended to undergo longer operations (196.6 ± 89.2 vs 177.2 ± 75.6 minutes, P = .087). Neurological functional recovery was lower with CS (mJOA [1.5 ± 3.6 vs 2.8 ± 2.7, P = .003]; Nurick [−0.8 ± 1.4 vs −1.5 ± 1.5, P = .002]), and CS was an independent predictor of worse mJOA recovery ratio at 2 years (B = −0.190, P < .0001). After propensity matching, improvement of neurological function was still lower in CS patients (mJOA [1.5 ± 3.6 vs 3.2 ± 2.8, P < .01]; Nurick [−0.8 ± 1.4 vs −1.4 ± 1.6, P = .02]). Conclusions: CS patients are older, present with worse neurological/functional impairment, and receive surgery on more levels and more commonly from the posterior. CS may indicate a more advanced state of DCM pathology and is more likely to result in a suboptimal surgical outcome.

A retrospective review of prospectively collected data.The purpose of this study is to compare and validate several preoperative scores for predicting outcomes following spine tumor resection.Preoperative risk assessment for patients undergoing spinal tumor resection remains challenging. At present, few risk assessment tools have been validated in this high-risk population.The 2008 to 2014 National Surgical Quality Improvement database was used to identify all patients undergoing surgical resection of spinal tumors, stratified as extradural, intradural extramedullary, and intramedullary based on CPT codes. American Society of Anesthesiologists (ASA) score, modified Charlson Comorbidity Index (CCI), and modified Frailty Index (mFI) were computed. A binary logistic regression model was used to explore the relationship between these variables and postoperative outcomes, including mortality, major and minor adverse events, and hospital length of stay (LOS). Other significant variables such as demographics, operative time, and tumor location were controlled for in each model.Two thousand one hundred seventy patients met the inclusion criteria. Higher CCI scores were independent predictors of mortality (OR = 1.24, 95% CI: 1.14-1.36, P 0.001), major adverse events (OR = 1.07, 95% CI: 1.01-1.31, P = 0.018), minor adverse events (OR = 1.15, 95% CI: 1.10-1.20, P 0.001), and prolonged LOS (OR = 1.14, 95% CI: 1.09-1.19, P 0.001). Patients' mFI scores were significantly associated with mortality and LOS, but not major or minor adverse events. ASA scores were not associated with any outcome metric when controlling for other variables.The CCI demonstrated superior predictive capacity compared with mFI and ASA scores and may be valuable as a preoperative risk assessment tool for patients undergoing surgical resection of spinal tumors. The validation of assessment scores is important for preoperative risk stratification and improving outcomes in this high-risk group.3.

The diagnosis of clear cell (CC) carcinoma of the endometrium can be challenging, especially when endometrioid (EC) and serous (SC) endometrial cancers exhibit nonspecific clear cell changes, in carcinomas with mixed histology and in the setting of Arias-Stella reaction (ASR). In this study, classic CC immunohistochemical markers (Napsin A, HNF-1β, and ER) and 2 recent novel markers, cystathionine gamma-lyase (CTH) and arginosuccinate synthase (ASS1), are assessed for their utility in distinguishing CC from its morphologic mimics. Tissue microarrays containing 64 CC, 128 EC, 5 EC with clear cell change, 16 SC, 5 mixed carcinomas, and 11 whole ASR sections were stained, with 12 additional examples of ASR stained subsequently. A cutoff of 70% and moderate intensity were used for HNF-1β, 80% of cells and strong intensity were used for CTH, and any staining was considered positive for the remaining markers. For differentiating CC from pure EC and SC, HNF-1β, Napsin A, and CTH all performed well. HNF-1β had higher specificity (99.3% vs. 95.1%) but lower sensitivity (55.8% vs. 73.1%) compared with Napsin A. CTH did not substantially outperform HNF- 1β or Napsin A (sensitivity 51.9%, specificity 99.3%). ASS1 and ER were not helpful (specificities of 60.1% and 22.6%). For differentiating CC from ASR, HNF-1β, Napsin A, and CTH stained a large proportion of ASR and were not useful. However, ER positivity and ASS1 negativity were helpful for identifying ASR (specificity 88.2% and 95.1%, respectively). EC with clear cell changes exhibited immunohistochemical patterns similar to pure EC (HNF-1β-, ER+, and CTH-). No markers were useful in confirming the CC components in mixed carcinomas.

Study Design: Retrospective cohort study. Objectives: To characterize regional variations in maximal nonoperative therapy (MNT) costs in patients suffering from lumbar stenosis or spondylolisthesis. Methods: Medical records from patients with symptomatic lumbar stenosis or spondylolisthesis undergoing primary ≤3-level lumbar decompression and fusion procedures from 2007 to 2016 were gathered from a large insurance database. Geographic regions (Midwest, Northeast, South, and West) reflected the US Census Bureau definitions. Records were searchable by International Classification of Diseases diagnosis/procedure codes, Current Procedural Terminology codes, and insurance-specific generic drug codes. Utilization of MNT, defined as cost billed, prescriptions written, and number of units disbursed, within 2-years prior to index surgery was assessed. Results: A total of 27 877 patients underwent 1-, 2-, or 3-level lumbar decompression and fusion surgery. Regional breakdown of the study cohort was as follows: South 62.3%, Midwest 25.2%, West 10.4%, Northeast 2.1%. Regional variations in the number of patients using nonsteroidal anti-inflammatory drugs (NSAIDs) ( P < .0001), opioids ( P < .0001), muscle relaxants ( P < .0001), and lumbar steroid injections ( P < .0001) were detected. A significant difference was identified in the regional MNT failure rates ( P < .0001). The total cost associated with MNT prior to index surgery was $48 411 125 ($1736.60/patient), with the Midwest ($1943.83/patient) responsible for the greatest average spending. Despite comprising 62.3% of the cohort, the South was accountable for 67.5% of NSAID prescriptions, 64.6% of opioid prescriptions, and 71.2% of muscle relaxant prescriptions. Conclusions: Regional differences exist in the costs of MNT in patients with lumbar stenosis and spondylolisthesis prior to surgery. Future studies should focus on identifying patients likely to fail prolonged nonoperative management.

Retrospective cohort study.The purpose of this study is to characterize the utilization and costs of MNTs prior to spinal fusion surgery in patients with symptomatic lumbar stenosis or spondylolisthesis.The costs and utilization of long-term maximal nonoperative therapy (MNT) can be substantial, and in the current era of bundled payments, the duration of conservative therapy trials should be reassessed.A large insurance database was queried for patients with symptomatic lumbar stenosis or spondylolisthesis undergoing index lumbar decompression and fusion procedures between 2007 and 2016. This database consists of 20.9 million covered lives and includes private/commercially insured and Medicare Advantage beneficiaries. Only patients with lumbar stenosis or spondylolisthesis and those continuously active within the insurance system for at least 5 years prior to the index operation were eligible.A total of 4133 out of 497,822 (0.8%) eligible patients underwent 1, 2, or 3-level posterior lumbar instrumented fusion. 20.8% of patients were smokers, 44.5% had type II DM, and 38.2% were obese (body mass index [BMI]30 kg/m). Patient MNT utilization was as follows: 66.7% used nonsteroidal anti-inflammatory drugs (NSAIDs), 84.4% used opioids, 58.6% used muscle relaxants, 65.5% received lumbar epidural steroid injections (LESI), 66.6% attended 21.1% presented to the emergency department (ED), and 24.9% received chiropractor treatments. The total direct cost associated with all MNT prior to index spinal fusion was $9,000,968; LESI comprised the largest portion of the total cost of MNT ($4,094,646, 45.5%), followed by NSAIDS ($1,624,217, 18.0%) and opioid costs ($1,279,219, 14.2%). At the patient level, when normalized per patient utilizing therapy, an average $4010 was spent on nonoperative treatments prior to index lumbar surgery.Assuming minimal improvement in pain and functional disability after maximum nonoperative therapies, the incremental cost-effectiveness ratio (ICER) for MNTs could be highly unfavorable.3.

Bartholin gland carcinomas are rare forms of vulvar malignancy and it is unclear what proportion is associated with high-risk human papilloma virus (HPV) infection. Our hospital archives were searched for all cases of Bartholin gland carcinoma from 1984 to 2017 (n=16). We excluded 3 adenoid cystic carcinomas, which were the subject of a previous study, leaving 13 cases. We reviewed all slides and performed immunostains for p16 as a surrogate biomarker for high-risk HPV. There were 12 squamous cell carcinomas (SCCs), including 1 SCC with transitional-like morphology and 1 papillary SCC, and 1 adenocarcinoma. All SCCs showed diffuse and intense p16 expression consistent with the presence of HPV. The single case of poorly differentiated adenocarcinoma showed patchy staining. Patient age ranged from 38 to 72 yr (mean, 58.3 yr). Most tumors were low stage. All patients were treated with radical vulvectomy and inguinofemoral lymphadenectomy. Mean clinical follow-up was 53.7 mo (range, 3-181 mo), 9 patients were free of disease (75%), recurrence occurred in 3 cases, with death due to disease in 2 of the patients with recurrence, including the single patient with adenocarcinoma. All SCC of Bartholin gland expressed p16 diffusely and intensely regardless of histologic features and grade. Our results support the etiologic role of HPV in the pathogenesis of SCC of Bartholin gland. In this small study we observed SCC as the predominant histotype, and most tumors presented at early stage and were associated with relatively favorable outcomes.

Study Design: Retrospective cohort study. Objectives: The purpose of this study is to characterize the utilization and costs of maximal nonoperative therapies (MNTs) within 2 years prior to spinal fusion surgery in patients with symptomatic lumbar stenosis or spondylolisthesis. Methods: A large insurance database was queried for patients with symptomatic lumbar stenosis or spondylolisthesis undergoing index 1-, 2-, or 3-level lumbar decompression and fusion procedures between 2007 and 2016. This database consists of 20.9 million covered lives and includes private/commercially insured and Medicare Advantage beneficiaries. The utilization of MNTs within 2 years prior to index surgery was assessed by cost billed to the patient, prescriptions written, and number of units billed. Results: A total of 27 877 out of 3 423 114 (0.8%) eligible patients underwent posterior lumbar instrumented fusion. Patient MNT utilization was as follows: 11 383 (40.8%) used nonsteroidal anti-inflammatory drugs (NSAIDs), 19 770 (70.9%) used opioids, 12 414 (44.5%) used muscle relaxants, 14 422 (51.7%) received lumbar epidural steroid injection (LESI), 11 156 (40.0%) attended physical therapy/occupational therapy, 4005 (14.4%) presented to the emergency department, and 4042 (14.5%) received chiropractor treatments. The total direct cost associated with all MNTs prior to index spinal fusion was $28 241 320 ($1013.07 per/patient). LESI comprised the largest portion of the total cost of MNT ($15 296 941, 54.2%), followed by opioids ($3 702 463, 13.1%) and NSAIDs ($3 058 335, 10.8%). Conclusions: Opioids are the most frequently prescribed and most used therapy in the preoperative period. Assuming minimal improvement in pain and functional disability after maximum nonoperative therapies, the incremental cost effectiveness ratio for MNT could be highly unfavorable.

Study Design:Focused literature review.Objective:The objective of this article was to help identify potential risk factors as well as strategies to help prevent surgical site infections (SSIs) in spine surgery.Methods:An article search was performed using PubMed, EMBASE, and the Cochrane database of systematic reviews using the terms “surgery” OR “surgical” AND “spine” OR “spinal” AND “infection”. Systematic review articles, meta-analyses, and clinical trials with more than 100 patients were reviewed.Results:Both patient and perioperative factors contribute to the development of SSIs. Patient factors such as smoking, obesity, diabetes, Methicillin-resistant Staphylococcus aureus (MRSA) colonization, and malnutrition are all modifiable risk factors that can lead to SSIs. Procedural steps, including preoperative MRSA screening and treatment for colonization, preoperative antibiotics, skin preparation, minimizing operative time, antibiotic or betadine irrigation, avoiding personnel turnover, and postoperative wound care have also been shown to decrease infection rates.Conclusion:There are several measures a spine practitioner may be able to take in the preoperative, intraoperative, and postoperative settings. Protocols to counsel patients regarding modification of preexisting risk factors and ensure adequate antimicrobial therapy in the perioperative period may be developed to reduce SSIs in spine surgery.

Stand-alone (SA) zero-profile implants are an alternative to cervical plating (CP) in anterior cervical discectomy and fusion (ACDF). In this study, we investigate differences in surgical outcomes between SA and CP in ACDF. We conducted a retrospective analysis of 166 patients with myelopathy and/or radiculopathy who had ACDF with SA or CP from Jan 2013–Dec 2016. We measured surgical outcomes including Bazaz dysphagia score at 3 months, Nurick grade at last follow-up, and length of hospital stay. 166 patients (92F/74M) were reviewed. 92 presented with radiculopathy (55%), 37 with myelopathy (22%), and 37 with myeloradiculopathy (22%). The average operative time with CP was longer than SA (194 ± 69 vs. 126 ± 46 min) (p &lt, 0.001), as was the average length of hospital stay (2.1 ± 2 vs. 1.5 ± 1 days) (p = 0.006). At 3 months, 82 patients (49.4%) had a follow-up for dysphagia, with 3 patients reporting mild dysphagia and none reporting moderate or severe dysphagia. Nurick grade at last follow-up for the myelopathy and myeloradiculopathy cohorts improved in 63 patients (85%). Prolonged length of stay was associated with reduced odds of having an optimal outcome by 0.50 (CI = 0.35–0.85, p = 0.003). Overall, we demonstrate that there is no significant difference in neurological outcome or rates of dysphagia between SA and CP, and that both lead to overall improvement of symptoms based on Nurick grading. However, we also show that the SA group has shorter length of hospital stay and operative time compared to CP.

Background The purpose of this study was to investigate the longitudinal postoperative relationship between physical activity, psychosocial factors, and physical function in patients undergoing lumbar spine surgery. Methods We enrolled 248 participants undergoing surgery for a degenerative lumbar spine condition. Physical activity was measured using a triaxial accelerometer (Actigraph GT3X) at 6-weeks (6wk), 6-months (6M), 12-months (12M) and 24-months (24M) following spine surgery. Physical function (computerized adaptive test domain version of Patient-Reported Outcomes Measurement Information System) and psychosocial factors (pain self-efficacy, depression and fear of movement) were assessed at preoperative visit and 6wk, 6M, 12M and 24M after surgery. Structural equation modeling (SEM) techniques were utilized to analyze data, and results are represented as standardized regression weights (SRW). Overall SRW were computed across five imputed datasets to account for missing data. The mediation effect of each psychosocial factor on the effect of physical activity on physical function were computed [(SRW for effect of activity on psychosocial factor X SRW for effect of psychosocial factor on function) ÷ SRW for effect of activity on function]. Each SEM model was tested for model fit by assessing established fit indexes. Results The overall effect of steps per day on physical function (SRW ranged from 0.08 to 0.19, pp Conclusions The findings of this study suggest that the relationship between physical activity and physical function is stronger than the relationship of function to activity. However, future research is needed to examine whether promoting physical activity during the early postoperative period may result in improvement of long-term physical function. Since depression and fear of movement had a very small mediating effect, additional work is needed to investigate other potential mediating factors such as pain catastrophizing, resilience and exercise self-efficacy.

Purpose/Objective(s) The COVID19 pandemic required radiation oncologists (ROs) to consider shorter treatment courses to minimize patient and staff exposure and conserve healthcare resources. Hematologic ROs adopted hypofractionated radiation therapy (hRT) regimens according to guidelines published by the International Lymphoma Radiation Oncology Group (ILROG). We report for the first time the preliminary efficacy and toxicity of these novel hypofractionated regimens in the treatment of hematologic malignancies. Materials/Methods We conducted a multicenter, multinational retrospective study under the direction of the ILROG. All patients receiving hRT according to ILROG guidelines from 1/1/2020 to 8/31/2020 were included. Patient and treatment details were abstracted from separate institutional databases. Toxicity was graded using CTCAE v5.0. Results Ninety-three patients from 4 institutions treated with 114 RT courses were included. Patient and treatment details are displayed in Table 1. Median follow up for the cohort was 179 days, and 77 patients (82%) were alive at last follow up. Maximal toxicity experienced by patients included Grade 1 (n = 16), Grade 2 (n = 1) and Grade 3 (n = 1) toxicities. Of 80 sites with response assessment within the RT field, 69% of patients achieved a complete response (n = 55), 20% partial response (n = 16), 9% stable disease (n = 7), and 2% progressive disease (n = 2). No COVID19 infections during or after RT have been documented in this patient cohort. Conclusion HRT according to ILROG guidelines resulted in low rates of acute toxicity and reasonable short-term treatment efficacy. Longer follow up and comparison with control groups is needed to draw more definitive conclusions and will be presented at the Annual Meeting.

BACKGROUND CONTEXT Engaging in physical activity early after lumbar spine surgery has promising effects on long-term postoperative recovery, including improved physical function. However, whether this effect is mediated through improvement in psychosocial factors is yet to be established. PURPOSE The purpose of this study was to investigate the longitudinal postoperative relationship between physical activity, psychosocial factors, and physical function in patients undergoing lumbar spine surgery. STUDY DESIGN/SETTING Secondary analysis from randomized controlled trial. PATIENT SAMPLE This study included 248 participants (mean ± SD; age=62.2±11.9 years; BMI=32.4±6.6 kg/m2 and 51% females) who underwent surgery for a degenerative lumbar spine condition. OUTCOME MEASURES Physical activity, defined as steps per day, was measured using a triaxial accelerometer (Actigraph GT3X) worn for >10 hours for >1 day(s) at 6 weeks (6wk), 6 months (6M), 12 months (12M) and 24 months (24M) following spine surgery. Physical function, measured with Patient-Reported Outcomes Measurement Information System, and psychosocial factors pain self-efficacy [Pain Self-Efficacy Questionnare], depression [Patient Health Questionnaire-9] and fear of movement [Tampa Scale for Kinesiophobia]) were assessed at preoperative visit and 6wk, 6M, 12M and 24M after surgery. METHODS Structural equation modeling (SEM) was used to analyze data and compute standardized coefficients to determine the effects of physical activity, function and psychosocial factors. Multiple imputation accounted for missing data and pooled coefficients and p-values were calculated using Rubin's approach. The mediation effect of each psychosocial factor on the effect of physical activity on physical function were computed by dividing the direct effects with the indirect effects. All SEM models controlled for age, employment, comorbidities, prior spine surgery, and preoperative pain self-efficacy, depression, fear of movement, physical function, and back and leg pain. Each SEM models was tested for model fit by assessing the established fit indexes. RESULTS The overall standardized direct effect of physical activity (ie, steps per day) on physical function ranged from 0.08 to 0.19 (p CONCLUSIONS The findings of this study support the use of early postoperative strategies to address physical activity in order to improve long-term physical function. Pain self-efficacy did not have a mediating effect while depression and fear of movement had a very small mediating effect; therefore, additional work is needed to investigate other potential mediating factors such as pain catastrophizing, resilience and exercise self-efficacy. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.